Genetic Variant NM_001170331.2:c.504C>T (chrX-37572374-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001170331.2(LANCL3):c.504C>T(p.Asp168Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,169,687 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 65 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., 26 hem., cov: 23)

Exomes 𝑓: 0.00014 ( 0 hom. 39 hem. )

Consequence

LANCL3
NM_001170331.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.172

Publications

1 publications found

Variant links:

Genes affected

LANCL3 (HGNC:24767): (LanC like family member 3) Predicted to be involved in carbohydrate metabolic process. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LANCL3 links:

ENSG00000250349 (HGNC:):

ENSG00000250349 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant X-37572374-C-T is Benign according to our data. Variant chrX-37572374-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2660281.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.172 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 26 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170331.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LANCL3	NM_001170331.2	MANE Select	c.504C>T	p.Asp168Asp	synonymous	Exon 1 of 5	NP_001163802.1	Q6ZV70-1
	LANCL3	NM_198511.3		c.504C>T	p.Asp168Asp	synonymous	Exon 1 of 6	NP_940913.1	Q6ZV70-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LANCL3	ENST00000378619.4	TSL:1 MANE Select	c.504C>T	p.Asp168Asp	synonymous	Exon 1 of 5	ENSP00000367882.4	Q6ZV70-1
LANCL3	ENST00000378621.7	TSL:1	c.504C>T	p.Asp168Asp	synonymous	Exon 1 of 6	ENSP00000367885.3	Q6ZV70-2
ENSG00000250349	ENST00000465127.1	TSL:5	c.171+146374C>T		intron	N/A	ENSP00000417050.1	B4E171

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

129

AN:

112164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00402

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000927

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.000660

GnomAD2 exomes

AF:

0.000372

AC:

AN:

113008

AF XY:

0.000180

show subpopulations

Gnomad AFR exome

AF:

0.00475

Gnomad AMR exome

AF:

0.000495

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000468

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000137

AC:

145

AN:

1057468

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

344968

show subpopulations

African (AFR)

AF:

0.00428

AC:

108

AN:

25261

American (AMR)

AF:

0.000313

AC:

AN:

28794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18678

East Asian (EAS)

AF:

0.00

AC:

AN:

27680

South Asian (SAS)

AF:

0.00

AC:

AN:

50171

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00000487

AC:

AN:

821470

Other (OTH)

AF:

0.000539

AC:

AN:

44562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00117

AC:

131

AN:

112219

Hom.:

Cov.:

AF XY:

0.000756

AC XY:

AN XY:

34381

show subpopulations

African (AFR)

AF:

0.00407

AC:

126

AN:

30928

American (AMR)

AF:

0.0000926

AC:

AN:

10796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3502

South Asian (SAS)

AF:

0.00

AC:

AN:

2676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53119

Other (OTH)

AF:

0.000652

AC:

AN:

1534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.00111

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.6

(source)

DANN

Benign

0.97

PhyloP100

-0.17

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over